Impaired humoral and cellular immunity after SARS-CoV-2 BNT162b2 (tozinameran) prime-boost vaccination in kidney transplant recipients

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1. Version published to 10.1172/jci150175

   Jul 15, 2021
2. 

   ScreenIT

   Apr 9, 2021

   SciScore for 10.1101/2021.04.06.21254963: (What is this?)

   Please note, not all rigor criteria are appropriate for all manuscripts.

   Table 1: Rigor

   Institutional Review Board Statement	not detected.
   Randomization	not detected.
   Blinding	not detected.
   Power Analysis	not detected.
   Sex as a biological variable	not detected.

   Table 2: Resources

   Antibodies
   Sentences	Resources
   The blocking ELISA based assay qualitatively detects anti-SARS-CoV2 antibodies inhibiting the interaction between receptor binding domain (RBD) of the viral spike glycoprotein and angiotensin-converting enzyme.	anti-SARS-CoV2 suggested: None
   Flow cytometric analysis: For detection of surface molecules, antibodies against CD3 (SK7, Biolegend, Carlsbad, CA, USA), CD4 (SK3, Becton Dickinson, Franklin Lakes, NJ, USA)	CD3 suggested: None CD4 suggested: None
   Software and Algorithms
   Sentences	Resources
   Follo…

   SciScore for 10.1101/2021.04.06.21254963: (What is this?)

   Please note, not all rigor criteria are appropriate for all manuscripts.

   Table 1: Rigor

   Institutional Review Board Statement	not detected.
   Randomization	not detected.
   Blinding	not detected.
   Power Analysis	not detected.
   Sex as a biological variable	not detected.

   Table 2: Resources

   Antibodies
   Sentences	Resources
   The blocking ELISA based assay qualitatively detects anti-SARS-CoV2 antibodies inhibiting the interaction between receptor binding domain (RBD) of the viral spike glycoprotein and angiotensin-converting enzyme.	anti-SARS-CoV2 suggested: None
   Flow cytometric analysis: For detection of surface molecules, antibodies against CD3 (SK7, Biolegend, Carlsbad, CA, USA), CD4 (SK3, Becton Dickinson, Franklin Lakes, NJ, USA)	CD3 suggested: None CD4 suggested: None
   Software and Algorithms
   Sentences	Resources
   Following adapter trimming, alignment to the GRCh38 reference genome obtained from ENSEMBL (38) was performed using STAR 2.7.1a (39) retaining only properly paired, uniquely mapping reads.	ENSEMBL suggested: (Ensembl, RRID:SCR_002344) STAR suggested: (STAR, RRID:SCR_004463)
   Count matrices were generated using featureCounts from subread 2.0.1 (40) with annotation version GRCh38.98 obtained from ENSEMBL.	featureCounts suggested: (featureCounts, RRID:SCR_012919)
   Downstream processing was performed using DESeq2 1.22.2 (41) in R 3.5.1.	DESeq2 suggested: (DESeq, RRID:SCR_000154)
   Differentially regulated pathways between groups were determined by Gene Set Enrichment Analysis (GSEA 4.1.0, (	GSEA suggested: (SeqGSEA, RRID:SCR_005724)
   FACS data analysis: FACS data were analyzed with FlowJo 10 (Becton Dickinson).	FlowJo suggested: (FlowJo, RRID:SCR_008520)
   Unsupervised analysis was conducted using t-distributed stochastic neighbor embedding (t-SNE) included in Cytobank (Beckman Coulter, Krefeld, Germany).	Cytobank suggested: (Cytobank, RRID:SCR_014043)
   Statistics: Statistical examination and composition of ELISA and FACS data derived graphs were executed using GraphPad Prism 8 (GraphPad, La Jolla, CA, USA).	GraphPad Prism suggested: (GraphPad Prism, RRID:SCR_002798) GraphPad suggested: (GraphPad Prism, RRID:SCR_002798)

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   Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

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   Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:

   Using comprehensive multiparameter analysis, our data further reveal significant limitations of vaccine-specific Th effector functions in these individuals, applying to all cytokines examined and equally affecting polyfunctionality. T cells secreting multiple effector molecules at a time have gained particular attention due to their association with superior viral control in HIV infected subjects (23) that was further verified for influenza infection (24). In context with vaccination, multipotent Th cells have been correlated with vaccine-induced immunity against tuberculosis (25). The presence of virus-reactive, multipotent T cells in convalescent seronegative individuals suggests a comparable role in protection against SARS-CoV2 (26), with possible implications for its absence in KTx patients. Extending flow cytometric data, low input transcriptome analysis of vaccine-specific T helper cells from transplant recipients highlighted downregulation of pathways involved in e.g. cellular activation, cytokine signalling and metabolism. Not surprisingly, these hallmarks represent footprints of immunosuppressive medication, as was e.g. shown for impaired IL-2-STAT5 signalling post kidney transplantation (27). Interestingly, IL-2 gene activity is also sensitive to TGFβ signalling (28), reflecting one of the features we found upregulated in Th cells from KTx patients. Amongst single genes, TNFSF4 (OX40L) showed increased transcript levels in this patient group; of note, OX40L protein ...

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   Results from TrialIdentifier: No clinical trial numbers were referenced.

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   Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

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   Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on page 27. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.

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   Results from rtransparent:

   • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
   • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
   • No protocol registration statement was detected.

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3. 

   Version published to 10.1101/2021.04.06.21254963v1 on medRxiv

   Apr 7, 2021